ABSTRACT RESEARCH SUMMARY: Maternal glucose-insulin homeostasis in pregnancy represents one of the most important physiological processes for maternal and child health outcomes. Although maternal diet is a key regulator of this process, its effects vary widely across individuals, suggesting other moderating factors may be at play. Based on studies that demonstrate diet and stress interact at various biological and behavioral levels, and the biological response to stress alters glucose-insulin homeostasis, I submit that stress likely represents a moderator of considerable significance in pregnancy. Yet, existing studies of pregnancy have not considered their combined effects. The primary goal of this K99/R00 project is to test the hypothesis that maternal prenatal stress may exacerbate the unfavorable effects of unhealthy diet on gestational glucose-insulin homeostasis. I aim to address this knowledge gap using two complementary approaches. Aim 1: To establish the independent effect of prenatal stress, and the interaction effect of prenatal diet quality and stress, on indicators of fasting insulin resistance (HOMA-IR and Adipo-IR). Aim 2: To conduct a randomized, controlled, cross-over study to experimentally test whether stress exposure potentiates the glycemic and fatty acid response to a standardized meal (indicative of postprandial insulin resistance) among pregnant women. CANDIDATE: My background expertise is maternal nutrition in pregnancy and the elucidation of prenatal factors that influence fetal development and child metabolic health. My research focus has now expanded to incorporate the role of prenatal stress and stress biology. My career goal is to develop and establish myself as an independent, trans- disciplinary investigator addressing key questions related to a) the combined effects of maternal diet and stress on pre-natal metabolism, and b) how prenatal biology may be altered via maternal behavior/psychosocial state for improved fetal programming outcomes. My short-term goals are a) to understand the prenatal biochemical effects of maternal diet-stress interplay, and b) to advance this field of research from observational to experimental study design. CAREER DEVELOPMENT PLAN: My training plan is designed to allow me to acquire the professional and technical skills necessary for a successful transition to independence as a trans-disciplinary investigator. It includes regular meetings, structured coursework, focused tutorials, practical training and research management under the guidance of an expert mentorship team, led by Pathik Wadhwa (prenatal stress, DOHaD), and co-mentors Sonja Entringer (fetal metabolic programming, stress biology), Janet King (prenatal nutrition, metabolism) and Daniel Gillen (biostatistics). ENVIRONMENT: The UC Irvine Development, Health and Disease Research Program (DHDRP) offers myriad resources, including an inter-disciplinary team to provide an intellectually productive environment, research staff, office, and laboratory facilities, and experiential training in state-of-the-art methods for studies of maternal-placental-fetal bi- ology, fetal development, and offspring body composition, metabolic function and brain development. The UCI Institute of Clinical and Translational Science, funded by the NIH Clinical & Translational Sciences Award program, provides expert support to junior scientists on research design, biostatistics, community engagement and bioassay platforms.